Reproductive health perspectives of young women with perinatally and behaviourally acquired HIV: A qualitative study.

Introduction: The aim of this study was to describe the sexual and reproductive goals of female adolescents with human immunodeficiency virus (HIV) in an urban cohort and decipher if they vary depending on the mode of HIV acquisition. Methods: We conducted in-depth qualitative interviews with 25 Black and/or Hispanic/Latinx female adolescents living with HIV (14 perinatally, 11 behaviourally acquired) aged 17-25 years who have access to care and antiretroviral therapy at an urban public hospitals (NYC, NY). Interviews were transcribed, coded and analysed using thematic analysis. Results: Interviews demonstrated that access to antiretroviral therapy and HIV disclosure to a sexual partner were critical aspects of sexual health for the majority of participants. Persons with perinatal HIV defined motherhood as a source of self-validation and were confident that antiretroviral therapy prevents HIV transmission. Persons with behaviourally acquired HIV viewed their status as an insurmountable barrier that will prevent them from attaining sexual intimacy with a partner and expressed persistent concerns about HIV transmission during pregnancy despite reassurance from medical providers. Conclusion: Sexual and reproductive perspectives of adolescents/young women living with HIV are multifactorial, highly stigmatized, and likely influenced by the mode of HIV acquisition. This population may benefit from patient-centred care models, including sexual health counselling that addresses sexual agency, intimacy, parenting and transmission risk reduction.

Partial treatment interruption of protease inhibitors augments HIV-specific immune responses in vertically infected pediatric patients.

BACKGROUND: Although highly active antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infected children, it often fails to completely suppress viral replication, thereby allowing the emergence of drug-resistant variants. Protease inhibitor (PI) based therapy has been hypothesized to depress cell-mediated immune responses by reducing antigen presentation. OBJECTIVES: To determine the effects of partial treatment interruption (PTI) of PI on HIV-specific cellular immune responses in children. METHODS: We conducted a retrospective longitudinal study of HIV-specific cellular immune responses in 13 children who were vertically infected with HIV. All had detectable plasma viremia and had undergone PTI for a median of 1.0 year (range, 0.41-3.35 years) while continuing nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor therapy. RESULTS: No significant changes in viral load were observed in the immediate time-point before and during PTI (P = 0.84) as well as in the overall period before and during PTI (P = 0.17). CD4 T-cell levels declined slowly immediately before and during PTI (P = 0.07) as well as during the overall PTI period (P = 0.0002), but the rate of CD4 T-cell decline was not significantly increased during PTI. Immediate to PTI, HIV-specific CD4 and CD8 T-cell responses increased by 70% (P < 0.0001) and 92% (P < 0.0001), respectively, and CD4 and CD8 T-cell activation levels (P = 0.6834 and P = 0.6081, respectively) remained unchanged. CONCLUSION: HIV-specific cellular immune responses are boosted in children who have interrupted PI-based therapy.

Association of differentiation state of CD4+ T cells and disease progression in HIV-1 perinatally infected children.

BACKGROUND: In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied. METHODOLOGY/PRINCIPAL FINDINGS: We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%≥25%) compared to those with severe immune suppression (LTS-SS; CD4%≤15%). Subjects in the LTS-NS group had significantly higher frequencies of naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RA-) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and <0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ T(EMRA) (CCR7-CD45RA+) cells compared to slow progressing subjects (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ T(EMRA) (CCR7-CD45RA+) cells.

Immunodominance of HIV-1 specific CD8+ T-cell responses is related to disease progression rate in vertically infected adolescents.

BACKGROUND: HIV-1 vertically infected children in the USA are living into adolescence and beyond with the widespread use of antiretroviral drugs. These patients exhibit striking differences in the rate of HIV-1 disease progression which could provide insights into mechanisms of control. We hypothesized that differences in the pattern of immunodomination including breadth, magnitude and polyfunctionality of HIV-1 specific CD8+ T cell response could partially explain differences in progression rate. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we mapped, quantified, and assessed the functionality of these responses against individual HIV-1 Gag peptides in 58 HIV-1 vertically infected adolescents. Subjects were divided into two groups depending upon the rate of disease progression: adolescents with a sustained CD4%≥25 were categorized as having no immune suppression (NS), and those with CD4%≤15 categorized as having severe immune suppression (SS). We observed differences in the area of HIV-1-Gag to which the two groups made responses. In addition, subjects who expressed the HLA- B*57 or B*42 alleles were highly likely to restrict their immunodominant response through these alleles. There was a significantly higher frequency of naïve CD8+ T cells in the NS subjects (p = 0.0066) compared to the SS subjects. In contrast, there were no statistically significant differences in any other CD8+ T cell subsets. The differentiation profiles and multifunctionality of Gag-specific CD8+ T cells, regardless of immunodominance, also failed to demonstrate meaningful differences between the two groups. CONCLUSIONS/SIGNIFICANCE: Together, these data suggest that, at least in vertically infected adolescents, the region of HIV-1-Gag targeted by CD8+ T cells and the magnitude of that response relative to other responses may have more importance on the rate of disease progression than their qualitative effector functions.

Strong HIV-1-specific T cell responses in HIV-1-exposed uninfected infants and neonates revealed after regulatory T cell removal.

BACKGROUND: In utero transmission of HIV-1 occurs on average in only 3%-15% of HIV-1-exposed neonates born to mothers not on antiretroviral drug therapy. Thus, despite potential exposure, the majority of infants remain uninfected. Weak HIV-1-specific T-cell responses have been detected in children exposed to HIV-1, and potentially contribute to protection against infection. We, and others, have recently shown that the removal of CD4(+) CD25(+) T-regulatory (Treg) cells can reveal strong HIV-1 specific T-cell responses in some HIV-1 infected adults. Here, we hypothesized that Treg cells could suppress HIV-1-specific immune responses in young children. METHODOLOGY/PRINCIPAL FINDINGS: We studied two cohorts of children. The first group included HIV-1-exposed-uninfected (EU) as well as unexposed (UNEX) neonates. The second group comprised HIV-1-infected and HIV-1-EU children. We quantified the frequency of Treg cells, T-cell activation, and cell-mediated immune responses. We detected high levels of CD4(+) CD25(+) CD127(-) Treg cells and low levels of CD4(+) and CD8(+) T cell activation in the cord blood of the EU neonates. We observed HIV-1-specific T cell immune responses in all of the children exposed to the virus. These T-cell responses were not seen in the cord blood of control HIV-1 unexposed neonates. Moreover, the depletion of CD4(+) CD25(+) Treg cells from the cord blood of EU newborns strikingly augmented both CD4(+) and CD8(+) HIV-1-specific immune responses. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that EU infants can mount strong HIV-1-specific T cell responses, and that in utero CD4(+) CD25(+) T-regulatory cells may be contributing to the lack of vertical transmission by reducing T cell activation.